Objective— High-density lipoprotein (HDL) is a heterogeneous lipoprotein class and there is no consensus on the value of HDL subspecies in coronary heart disease (CHD) risk assessment. We tested the hypothesis whether specific HDL subpopulations are significantly associated with CHD-prevalence.

Methods and Results— ApoA-I concentrations (mg/dL) in HDL subpopulations were quantitatively determined by native 2d gel electrophoresis, immunoblotting, and image analysis in male participants in the Framingham Offspring Study (FOS). CHD cases (n=169) had higher preβ-1 and α-3 particle and lower α-1, preα-3, and preα-1 particle levels than either all (n=1277) or HDL cholesterol-matched (n=358) controls. α-1 and preα-3 levels had an inverse association, whereas α-3 and preα-1 particle levels had a positive association with CHD prevalence after adjusting the data for established CHD risk factors. Standardized logit coefficients indicated that α-1 HDL was most significantly associated with CHD prevalence. Moreover, each mg/dL increase in α-1 particle level decreased odds of CHD by 26% (P<0.0001), whereas each mg/dL increase in HDL cholesterol decreased odds of CHD by 2% in a model including all established CHD risk factors.

Conclusions— Specific HDL subpopulations were positively correlated, whereas others were inversely correlated with CHD prevalence in male subject in the FOS, indicating that the various HDL particles might have different roles in the cause of CHD.